Abstract

Anesth Analg. 2010 Jun;110(6):1597-606. Epub 2010 Apr 30.

Propofol reduces the distribution and clearance of midazolam.

Authors: Lichtenbelt BJ, Olofsen E, Dahan A, van Kleef JW, Struys MM, Vuyk J.

Department of Anesthesiology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. j.vuyk@lumc.n.

Background
Midazolam, at sedative levels, increases blood propofol concentrations by 25%. We evaluated the reverse interaction and determined the influence of propofol on the pharmacokinetics of midazolam.

Methods
Eight healthy male volunteers were studied on 2 occasions in a random crossover manner. During session A, volunteers received midazolam 0.035 to 0.05 mg . kg(-1) IV for 1 minute followed by an infusion of 0.035 to 0.05 mg . kg(-1) . h(-1) for 59 minutes. During session B, in addition to this midazolam infusion scheme, a target-controlled infusion of propofol (constant C(T): 0.6 or 1.0 mug . mL(-1)) was given from 15 minutes before the start until 6 hours after termination of the midazolam infusion. Arterial blood samples for propofol and midazolam concentration analysis were taken until 6 hours after termination of the midazolam infusion. Nonlinear mixed-effect models examining the influence of propofol and hemodynamic variables on midazolam pharmacokinetics were constructed using Akaike's information-theoretic criterion for model selection.

Results
In the presence of a mean blood propofol concentration of 1.2 mug . mL(-1), the plasma midazolam concentration was increased by 26.9% +/- 9.4% compared with midazolam given as a single drug. Propofol (C(blood): 1.2 mug . mL(-1)) reduced midazolam central volume of distribution from 5.37 to 2.98 L, elimination clearance from 0.39 to 0.31 L . min(-1), and rapid distribution clearance from 2.77 to 2.11 L . min(-1). Inclusion of heart rate further improved the pharmacokinetic model of midazolam.

Conclusions
Propofol reduces the distribution and clearance of midazolam in a concentration-dependent manner. In addition, inclusion of heart rate as a covariate improved the pharmacokinetic model of midazolam predominantly through a reduction in the intraindividual variability.

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Rev Col Bras Cir. 2010 Feb;37(1):10-6.

Comparative study of efficacy and safety between propofol and midazolam for sedation during colonoscopy

Authors: Ivano FH, Romeiro PC, Matias JE, Baretta GA, Kay AK, Sasaki CA, Nakamoto R, Tambara EM.

Programa de Pós-Graduação em Clínica Cirúrgica, Universidade Federal do Paraná, Curitiba, PR, BR.

Objective
To compare safety and efficacy of propofol with midazolam for deep sedation in the colonoscopy.

Methods
In a prospective way, 66 patients underwent colonoscopy--50 patients received propofol in an average dose of 3,25 mgxkg-1 and 16 patients (control group) received midazolam with total average dose of 2,05 mgxkg-1. The dose of medication was titrated according to patient need. The analyzed cardiovascular and respiratory parameters were: oxygen saturation, systolic and diastolic blood pressure and heart rate. After the colonoscopy, a survey with a visual scale from 0 to 10 and questions regarding the pain, discomfort and satisfaction was applied. The statistics analyzed by the t Student test.

Results
Groups were similar regarding the age, weight, sex and physical conditions (ASA grade). None of the patient required emergencial treatment. None of the cardiovascular and respiratory parameters with statistics differences produced hemodynamic repercussions. The pain and satisfaction parameters showed no significant difference between the midazolam group and propofol group The discomfort parameter during the colonoscopic showed significant difference (p=0,038) between the midazolam group (score 2,81) and propofol group (score 1,18) and all the patients which had presented paradoxal excitation (25%) in this group reported discomfort.

Conclusions
The cardiovascular and respiratory parameters variation, even when different between groups, didn't produced clinical repercussions. The pain and satisfaction parameters showed no significant difference between groups. It was demonstrated that the midazolam group referred more discomfort than the propofol group.

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